Effervescent compositions usually comprise excipients, active ingredients, and a source of carbon dioxide typically referred to as an effeverscent couple. Effervescent couples are usually composed of an alkaline bicarbonate or carbonate and an acid. In the presence of water, the alkaline bicarbonate or carbonate and the acid generate carbon dioxide. Thus, effeverscent compositions are extremely sensitive to moisture. This necessitates special steps to protect the raw materials and the finished formulation from exposure to moisture, throughout the manufacturing process and thereafter. Anhydrous citric acid is the most commonly employed acidulant in the manufacture of effeverscent compositions. Anhydrous citric acid is however, extremely hygroscopic. So also are the most commonly employed sources of carbon dioxide, i.e, alkali bicarbonates and carbonates.
The aforementioned problems are compounded when an effervescent composition is to contain, as the active, a histamine H.sub.2 antagonist. Histamine H.sub.2 antagonists are incompatible with acids, particularly the acids employed in effervescent compositions. Published EP Patent specification No. 233853 discloses that use of citric acid in effervescent compositions containing a histamine H.sub.2 antagonist evidences incompatibility of the H.sub.2 antagonist with the acids contained in the effervescent composition. In an effort to resolve this, citric acid was replaced by a mixture of mono- and di- alkaline citrates.
U.S. Pat. No. 4,824,664 teaches that histamine H.sub.2 antagonists are not stable with the acids contained in effervescent products. They endeavor to overcome this instability by granulating the effervescent mixture and generating during such granulation a mixture of mono- and di- alkali citrate in a specified ratio.
U.S. Pat. No. 5,102,665 teaches preparation of a stable effervescent ranitidine using mono-alkali citrate as the sole acidulant. The effervescent system disclosed therein is granulated in alcohol prior to manufacturing the composition.